The tachykinins include the naturally-occurring neuropeptides substance P, neurokinin A and neurokinin B. The tachykinins act as agonists of receptors occurring in larger mammals and humans, such as the neurokinin (NK) 1, 2 and receptors. Artificially prepared compounds which are antagonistic to tachykinin receptors are usually classified according to their relative ability to bind to one or more of the aforementioned three receptor subtypes. In the physiological process the tachykinins play an important part in the transmission of pain, emesis, neurogenic inflammations, bladder inflammation, inflammatory joint diseases or asthmatic complaints.
Piperazine derivatives which act as antagonists to the NK1 receptor are known from U.S. Patent Publication No. 2004/03428 (=WO 2004/033428). Piperazine derivatives which act as antagonists to the NK2 receptor are known from U.S. Pat. No. 6,770,649 (=EP 1,293,506). Piperazine derivatives which can act as antagonists to tachykinin receptors are known from U.S. Pat. No. 5,607,936 (=WO 96/10568).
It would be desirable to have new active substances having properties antagonistic to tachykinin receptors NK1 and NK2, which are suitable in particular for the treatment and/or inhibition of respiratory diseases, in particular asthma, bronchitis, cough, and rhinitis; skin diseases, in particular inflammatory skin reactions, allergic skin reactions, and psoriasis; arthropathic diseases, in particular arthritis, vasculitides and systemic lupus erythematosus; functional or inflammatory disorders in the gastrointestinal tract, in particular pseudomembranous colitis and diarrhea; bleb diseases such as cystitis and interstitial cystitis; and migraine.